Early reporting for cancer screening trials.
OBJECTIVE
Many cancer screening trials involve a screening programme of one or more screenings with follow-up after the last screening. Usually a maximum follow-up time is selected in advance. However, during the follow-up period there is an opportunity to report the results of the trial sooner than planned. Early reporting of results from a randomized screening trial is important because obtaining a valid result sooner translates into health benefits reaching the general population sooner. The health benefits are reduction in cancer deaths if screening is found to be beneficial and more screening is recommended, or avoidance of unnecessary biopsies, work-ups and morbidity if screening is not found to be beneficial and the rate of screening drops.


METHODS
Our proposed method for deciding if results from a cancer screening trial should be reported earlier in the follow-up period is based on considerations involving postscreening noise. Postscreening noise (sometimes called dilution) refers to cancer deaths in the follow-up period that could not have been prevented by screening: (1) cancer deaths in the screened group that occurred after the last screening in subjects whose cancers were not detected during the screening program and (2) cancer deaths in the control group that occurred after the time of the last screening and whose cancers would not have been detected during the screening programme had they been randomized to screening (the number of which is unobserved). Because postscreening noise increases with follow-up after the last screening, we propose early reporting at the time during the follow-up period when postscreening noise first starts to overwhelm the estimated effect of screening as measured by a z-statistic. This leads to a confidence interval, adjusted for postscreening noise, that would not change substantially with additional follow-up. Details of the early reporting rule were refined by simulation, which also accounts for multiple looks.


RESULTS
For the re-analysis of the Health Insurance Plan trial for breast cancer screening and the Mayo Lung Project for lung cancer screening, estimates and confidence intervals for the effect of screening on cancer mortality were similar on early reporting and later.


CONCLUSIONS
The proposed early reporting rule for a cancer screening trial with post-screening follow-up is a promising method for making results from the trial available sooner, which translates into health benefits (reduction in cancer deaths or avoidance of unnecessary morbidity) reaching the population sooner.
Baker
Stuart G
SG
Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892-7354, USA. sb16i@nih.gov
Kramer
Barnett S
BS
Prorok
Philip C
PC
D002986:Clinical Trials as Topic; D018563:Disease Notification / Q000706:statistics & numerical data; D055088:Early Detection of Cancer; D006801:Humans; D007348:Insurance, Health / Q000191:economics; D008403:Mass Screening / Q000379:methods*; D009369:Neoplasms / Q000191:economics / Q000453:epidemiology* / Q000401:mortality; D010349:Patient Compliance / Q000706:statistics & numerical data; D016012:Poisson Distribution; D014481:United States / Q000453:epidemiology